OBJECTIVE: Define in a systematic fashion the structural parameters of antigenic determinants on a globular protein which affect the immune response, in terms of the similarities and differences between the immunogen and the homologous protein of the host. APPROACH: Cytochrome c presents an ideal model system for the envisaged studies, since all eukaryotic cytochromes c have identical spatial conformations and surface residue changes cause only local changes in topography. By immunizing rabbits and mice against a variety of cytochromes c having only relatively few amino acid sequence varieties from the cytochrome c of the hosts, relatively simple humoral responses should ensue. These should be readily amenable to analysis into single-site antibody populations which can be isolated and whose properties can be determined and related to the structure of the corresponding antigenic determinants. Conceptually similar approaches to T-cell mediated phenomena which distinguish between the contributions of various antigenic determinants on the immunogen should make it possible to determine whether the same determinants and the same efforts occur with this class of immune systems.